Dokument: Off-pathway oligomers of α-synuclein and Aβ inhibit secondary nucleation of α-synuclein amyloid fibrils
| Titel: | Off-pathway oligomers of α-synuclein and Aβ inhibit secondary nucleation of α-synuclein amyloid fibrils | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=69201 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250401-092941-4 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Schützmann, Marie P. [Autor] Hoyer, Wolfgang [Autor] | |||||||
| Dateien: |
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| Stichwörter: | amyloid aggregation, α-synuclein, oligomers, Aβ cross-seeding, protofibrils | |||||||
| Beschreibung: | Synuclein ( yn) is a key culprit in the pathogenesis of synucleinopathies such as Parkinson’s Disease (PD), in which it forms not only insoluble aggregates called amyloid fibrils but also smaller, likely more detrimental species termed oligomers. This property is shared with other amyloidogenic proteins such as the Alzheimer’s Disease-associated amylo b b). We previously found an intriguing interplay between off-pathway A oligomers andfibrils, in which the oligomers interfere with fibril formation via inhibition of secondary nucleation by blocking secondary nucleation sites on the fibril surface. Here, using ThT aggregation kinetics and atomic force microscopy (AFM), we tested if the same interplay applies toyn fibrils. Both homotypic (i.e. a n) and heterotypic (i.e. Ab)-pathway oligomers inhibited yn aggregation in kinetic assays of secondary nucleation. Initially soluble, kinetically trapped Ab igo-mers co-precipitated with Syn(1–108) fibrils. The resulting co-assemblies were imaged as clusters of curvilinear oligomers by AFM. The results indicate that off-pathway oligomers have a general tendency to bind amyloid fibril surfaces, also in the absence of sequence homology between fibril and oligomer. The interplay between off-pathway oligomers and amyloid fibrils adds another level of complexity to the homo-and hetero-assembly processes of amyloidogenic proteins | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Schützmann, M., & Hoyer, W. (2025). Off-pathway oligomers of α-synuclein and Aβ inhibit secondary nucleation of α-synuclein amyloid fibrils. Journal of Molecular Biology, 437(10), Article 169048. https://doi.org/10.1016/j.jmb.2025.169048 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 01.04.2025 | |||||||
| Dateien geändert am: | 01.04.2025 |
